Adaptation of Skeletal Muscle O2 Transport and Utilization in Rats with Right Heart Failure

Abstract

Exercise intolerance is a cardinal symptom in patients with heart failure (HF), resulting from energetic failure in both cardiac and skeletal muscles. HF is known to be associated with skeletal muscle atrophy and a shift towards fast fatigable fibers (Vescovo et al. Int J Cardiol 104:298-, 2005). Additionally, right HF is associated with peripheral edema which may impair convective and diffusive O2 transport. However, structural changes in the pathways determining diffusive O2 transport and utilization are not well understood in right HF. PURPOSE: We therefore determined capillarization, oxidative enzyme activity, fiber area and type in skeletal muscle from rats with right HF. METHODS: Right ventricle hypertrophy was induced by monocrotaline treatment (MCT; 60 mg/kg) in 6 rats, compared to saline control (CON; n=6). After 23±1 (mean, SD) days decompensated HF was verified by weight loss and clinical symptoms. Serial sections (10 μm) of the plantaris muscle were stained for ATPase activity (fiber type), succinate dehydrogenase (SDH) activity (oxidative capacity) and capillaries. Glycolytic and oxidative regions were analyzed separately and compared between conditions by two-way ANOVA. RESULTS: In MCT whole body and liver weights were less (p<0.01), and right ventricle and lung weights were greater (p<0.01) than CON. The plantaris was heavier in CON than MCT: 273±19 vs. 242±5 mg (p<0.05); but mean fiber cross-sectional area was not different: 2143±405 vs. 2045±287 μm2. The area occupied by type IIa fibers tended to be lower and the area of hybrid (IIa/x) fibers was significantly greater (p<0.05) in MCT. SDH activity was 15% lower in MCT independent of region and fiber type (p=0.06) and capillary to fiber ratio was greater in CON than MCT: 2.3±0.3 vs. 1.9±0.2 (p<0.05). CONCLUSIONS: As expected, there was a shift towards fast fatigable fibers in MCT treated rats. However, there was a similar reduction in SDH activity in both oxidative and glycolytic regions independent of fiber type, suggesting different remodeling pathways. The lower oxidative capacity in MCT was concurrent with a lower potential for diffusive O2 transport, as evidenced by fewer capillaries per fiber, but without fiber atrophy. These reductions in diffusive O2 transport and utilization may contribute to the energetic failure of skeletal muscles in right HF.